Skip to main content
SpringerLink
Log in

Hereditary Ovarian Cancer

  • Chapter
  • First Online:
Hereditary Breast and Ovarian Cancer

  • 498 Accesses

Abstract

The treatment of ovarian cancer has changed significantly over the past few years, particularly in the case of hereditary breast and ovarian cancer (HBOC) syndrome. Genetic testing for BRCA1 and BRCA2 is used not only for a diagnosis for HBOC but also a biomarker for PARP inhibitors, which is of great importance in the treatment of ovarian cancer. The characteristics of ovarian cancer in HBOC have been reported of the highest prevalence in high-grade serous carcinoma subtype, high sensitivity to platinum salt chemotherapies and PARP inhibitors, and a better prognosis compared to BRCA-negative ovarian cancer. It is important to note that ovarian cancer with a family history is also associated with Lynch syndrome, although less frequently than HBOC. In addition, recent multi-panel genetic analysis has led to the identification of genes other than HBOC that are involved in the development of ovarian cancer, which may require further clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Goff BA, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007;109(2):221–7. https://doi.org/10.1002/cncr.22371.

    Article  PubMed  Google Scholar 

  3. Gilbert L, et al. Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol. 2012;13(3):285–91. https://doi.org/10.1016/S1470-2045(11)70333-3.

    Article  PubMed  Google Scholar 

  4. Lim AWW, et al. Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes. J Natl Cancer Inst. 2012;104:114–24. https://doi.org/10.1093/jnci/djr486.

    Article  PubMed  Google Scholar 

  5. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer version 1. 2020.

    Google Scholar 

  6. Wentzensen N, et al. Ovarian cancer risk factors by histologic subtype: an analysis from the ovarian cancer cohort consortium. J Clin Oncol. 2016;34(24):2888–98. https://doi.org/10.1200/JCO.2016.66.8178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Takano M, Tsuda H, Sugiyama T. Clear cell carcinoma of the ovary: is there a role of histology-specific treatment? J Exp Clin Cancer Res. 2012; https://doi.org/10.1186/1756-9966-31-53.

  8. Buys SS, et al. Effect of screening on ovarian cancer mortality: the prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA. 2011;305(22):2295–302. https://doi.org/10.1001/jama.2011.766.

    Article  CAS  PubMed  Google Scholar 

  9. Jacobs IJ, et al. Ovarian cancer screening and mortality in the UK collaborative trial of ovarian Cancer screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387(10022):945–56. https://doi.org/10.1016/S0140-6736(15)01224-6.

    Article  PubMed  PubMed Central  Google Scholar 

  10. JSGO Guidelines. Guidelines for treatment of ovarian cancer, fallopian tube cancer and primary peritoneal cancer. 2020 edition. Japan Society of Gynecologic Oncology (JSGO); 2020.

    Google Scholar 

  11. Bristow RE, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248–59. https://doi.org/10.1200/jco.2002.20.5.1248.

    Article  PubMed  Google Scholar 

  12. Panici PB, et al. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst. 2005;97(8):560–6. https://doi.org/10.1093/jnci/dji102.

    Article  PubMed  Google Scholar 

  13. Harter P, et al. A randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. N Engl J Med. 2019;380(9):822–32. https://doi.org/10.1056/nejmoa1808424.

    Article  PubMed  Google Scholar 

  14. Burger RA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–83. https://doi.org/10.1056/nejmoa1104390.

    Article  CAS  PubMed  Google Scholar 

  15. Perren TJ, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–96. https://doi.org/10.1056/nejmoa1103799.

    Article  CAS  PubMed  Google Scholar 

  16. Moore K, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495–505. https://doi.org/10.1056/nejmoa1810858.

    Article  CAS  PubMed  Google Scholar 

  17. Coleman RL, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381(25):2403–15. https://doi.org/10.1056/nejmoa1909707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. González-Martín A, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391–402. https://doi.org/10.1056/nejmoa1910962.

    Article  CAS  PubMed  Google Scholar 

  19. Ray-Coquard I, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416–28. https://doi.org/10.1056/nejmoa1911361.

    Article  CAS  PubMed  Google Scholar 

  20. Aghajanian C, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30(17):2039–45. https://doi.org/10.1200/JCO.2012.42.0505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Coleman RL, Brady MF, et al. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG oncology/gynecologic oncology group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(6):779–91. https://doi.org/10.1016/S1470-2045(17)30279-6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Coleman RL, Oza AM, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949–61. https://doi.org/10.1016/S0140-6736(17)32440-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ledermann J, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382–92. https://doi.org/10.1056/nejmoa1105535.

    Article  CAS  PubMed  Google Scholar 

  24. Ledermann J, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014;15(8):852–61. https://doi.org/10.1016/S1470-2045(14)70228-1.

    Article  CAS  PubMed  Google Scholar 

  25. Mirza MR, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154–64. https://doi.org/10.1056/nejmoa1611310.

    Article  CAS  PubMed  Google Scholar 

  26. Pujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302–8. https://doi.org/10.1200/JCO.2013.51.4489.

    Article  CAS  PubMed  Google Scholar 

  27. Norquist BM, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016;2(4):482. https://doi.org/10.1001/jamaoncol.2015.5495.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hirasawa A, et al. Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. Oncotarget. 2017;8(68):112258–67. https://doi.org/10.18632/oncotarget.22733.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bowtell DD, et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2015;15(11):668–79. https://doi.org/10.1038/nrc4019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kurian AW, et al. Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precis Oncol. 2017;1:1–12. https://doi.org/10.1200/po.16.00066.

    Article  PubMed  Google Scholar 

  31. Lilyquist J, et al. Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. Gynecol Oncol. 2017;147(2):375–80. https://doi.org/10.1016/j.ygyno.2017.08.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Loveday C, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011;43(9):879–82. https://doi.org/10.1038/ng.893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Loveday C, et al. Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat Genet. 2012;44(5):475–6. https://doi.org/10.1038/ng.2224.

    Article  CAS  PubMed  Google Scholar 

  34. Rafnar T, et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat Genet. 2011;43(11):1104–7. https://doi.org/10.1038/ng.955.

    Article  CAS  PubMed  Google Scholar 

  35. Ramus SJ, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. J Natl Cancer Inst. 2015;107(11) https://doi.org/10.1093/jnci/djv214.

  36. Song H, et al. Contribution of germline mutations in the RAD51B, RAD51C, and RAD51D genes to ovarian cancer in the population. J Clin Oncol. 2015;33(26):2901–7. https://doi.org/10.1200/JCO.2015.61.2408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lu HM, et al. Association of Breast and Ovarian Cancers with predisposition genes identified by large-scale sequencing. JAMA Oncol. 2019;5(1):51–7. https://doi.org/10.1001/jamaoncol.2018.2956.

    Article  PubMed  Google Scholar 

  38. Masuda K, et al. Clinical utility of a self-administered questionnaire for assessment of hereditary gynecologic cancer. Jpn J Clin Oncol. 2017;47(5):401–6. https://doi.org/10.1093/jjco/hyx019.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Alsop K, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian ovarian cancer study group. J Clin Oncol. 2012;30(21):2654–63. https://doi.org/10.1200/JCO.2011.39.8545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Risch HA, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98(23):1694–706. https://doi.org/10.1093/jnci/djj465.

    Article  CAS  PubMed  Google Scholar 

  41. Enomoto T, et al. The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to ovarian cancer geneTic TEsting of BRCA (CHARLOTTE). Int J Gynecol Cancer. 2019;29(6):1043–9. https://doi.org/10.1136/ijgc-2019-000384.

    Article  PubMed  Google Scholar 

  42. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. 2020.

    Google Scholar 

  43. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–33. https://doi.org/10.1200/JCO.2006.09.1066.

    Article  PubMed  Google Scholar 

  44. Kuchenbaecker KB, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402–16. https://doi.org/10.1001/jama.2017.7112.

    Article  CAS  PubMed  Google Scholar 

  45. Rebbeck TR, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA. 2015;313(13):1347–61. https://doi.org/10.1001/jama.2014.5985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4(9):665–76. https://doi.org/10.1038/nrc1431.

    Article  CAS  PubMed  Google Scholar 

  47. Callahan MJ, et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol. 2007;25(25):3985–90. https://doi.org/10.1200/JCO.2007.12.2622.

    Article  PubMed  Google Scholar 

  48. Powell BC, et al. Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol. 2005;23(1):127–32. https://doi.org/10.1200/JCO.2005.04.109.

    Article  PubMed  Google Scholar 

  49. Powell CB, et al. Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol. Int J Gynecol Cancer. 2011;21(5):846–51. https://doi.org/10.1097/IGC.0b013e31821bc7e3.

    Article  PubMed  Google Scholar 

  50. Shaw PA, et al. Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers. Mod Pathol. 2009;22(9):1133–8. https://doi.org/10.1038/modpathol.2009.89.

    Article  CAS  PubMed  Google Scholar 

  51. Medeiros F, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30(2):230–6. https://doi.org/10.1097/01.pas.0000180854.28831.77.

    Article  PubMed  Google Scholar 

  52. Lee Y, et al. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J Pathol. 2007;211(1):26–35. https://doi.org/10.1002/path.2091.

    Article  CAS  PubMed  Google Scholar 

  53. Bolton KL, et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA. 2012;307(4):382–90. https://doi.org/10.1001/jama.2012.20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Candido-dos-Reis FJ, et al. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clin Cancer Res. 2015;21(3):652–7. https://doi.org/10.1158/1078-0432.CCR-14-2497.

    Article  CAS  PubMed  Google Scholar 

  55. Gallagher DJ, et al. Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity. Ann Oncol. 2011;22(5):1127–32. https://doi.org/10.1093/annonc/mdq577.

    Article  CAS  PubMed  Google Scholar 

  56. Vencken PMLH, et al. Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients. Ann Oncol. 2011;22(6):1346–52. https://doi.org/10.1093/annonc/mdq628.

    Article  CAS  PubMed  Google Scholar 

  57. Yang D, et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA. 2011;306(14):1557–65. https://doi.org/10.1001/jama.2011.1456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pennington KP, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20(3):764–75. https://doi.org/10.1158/1078-0432.CCR-13-2287.

    Article  CAS  PubMed  Google Scholar 

  59. Miller RE, et al. ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer. Ann Oncol. 2020; https://doi.org/10.1016/j.annonc.2020.08.2102.

  60. Meric-Bernstam F, et al. Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol. Ann Oncol. 2016;27(5):795–800. https://doi.org/10.1093/annonc/mdw018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Rosenthal AN, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom familial ovarian cancer screening study. J Clin Oncol. 2017;35(13):1411–20. https://doi.org/10.1200/JCO.2016.69.9330.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Skates SJ, et al. Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – combined results from two screening trials. Clin Cancer Res. 2017;23(14):3628–37. https://doi.org/10.1158/1078-0432.CCR-15-2750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Helder-Woolderink JM, et al. Ovarian cancer in lynch syndrome; a systematic review. Eur J Cancer. 2016;55:65–73. https://doi.org/10.1016/j.ejca.2015.12.005.

    Article  CAS  PubMed  Google Scholar 

  64. Akbari MR, et al. Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens. Familial Cancer. 2017;16(3):351–5. https://doi.org/10.1007/s10689-017-9973-1.

    Article  CAS  PubMed  Google Scholar 

  65. Tung N, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13:581–8. https://doi.org/10.1038/nrclinonc.2016.90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan

    Kenta Masuda, Megumi Satake & Daisuke Aoki

Authors
  1. Kenta Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Megumi Satake
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenta Masuda .

Editor information

Editors and Affiliations

  1. Department of Breast Surgical Oncology, Showa University, School of Medicine, Tokyo, Japan

    Seigo Nakamura

  2. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan

    Daisuke Aoki

  3. Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Yoshio Miki

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Masuda, K., Satake, M., Aoki, D. (2021). Hereditary Ovarian Cancer. In: Nakamura, S., Aoki, D., Miki, Y. (eds) Hereditary Breast and Ovarian Cancer . Springer, Singapore. https://doi.org/10.1007/978-981-16-4521-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-16-4521-1_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-4520-4

  • Online ISBN: 978-981-16-4521-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation